In 1979, the mechanism of chemical carcinogenesis, a challenging anddifficult scientific problem pending for a number of years, was explained by Dai Qianhuan. Themechanism named di-region theory predicted that a carci...In 1979, the mechanism of chemical carcinogenesis, a challenging anddifficult scientific problem pending for a number of years, was explained by Dai Qianhuan. Themechanism named di-region theory predicted that a carcinogen always metabolizes to form a specialbi-functional alky-lating agent. This agent induces cross-linkages between the complementary basepairs in DMA and switches on initial mutageneses in genomes including point and frameshiftmutations. This, in turn, induces further deep mutageneses including the production of variouschimeric chromosomes, deletions and other aberrations found in genomes. In the end this initiatescarcinogenesis of the whole cell through the reverse transcription mechanism after a lengthyincubation period. Recently, this laboratory has verified that physical carcinogenesis, includingthe oncogenesis induced by radiation and asbestos as well as the carcinogenesis induced byendogenous factors such as estrogen or diethyl-stilbestrol switch on carcinogenesis by inducing theformation of cross-linkages between the complementary base pairs in DNA. Di-region theory has nowbeen supported by many experimental observations such as mutational spectra of various carcinogens.The potential for carcinogenesis, teratogenesis, sterility and mutagenesis lumped together asgenetic toxicity appears to originate almost uniformly from the cross-linking between complementarybases, i.e. malignant cross-linking, which is in accordance with di-region theory. Other forms ofcross-linking between non-complementary bases, benign cross-linkings, show bi-functional alkylationanticancer activity but lack genetic toxicity. The predictable design and synthesis of a highselectivity anticancer agent with high efficacy and low genetic toxicity, a goal long pursued incancer chemotherapy, have been realized for the first time in this laboratory by inhibitingmalignant and heightening benign cross-linking using the principles of di-region theory. A series ofpatented new anticancer platinum complexes called di-regioplatins, based on the above predetermineddesign, have been reported. In these cancer cell kill rates, tumor-inhibition rates and theultimate life-span for two mouse carcinoma models using several compounds ofcis-di-substituted-benzylaminodihaloplatinum (II) are notably higher than those of cisplatin, buttheir toxicities all are much lower than cisplatin. Based on a predictive design using di-regiontheory and group theory, a new anticancer complex,cis-diammine-cyclopentane-1,1-dicarboxylato-platinum (II) called minoplatin, has been synthesized inthis laboratory by making the minimal structural revision of adding an CH_2 unit on the four-memberring of carboplatin.展开更多
文摘In 1979, the mechanism of chemical carcinogenesis, a challenging anddifficult scientific problem pending for a number of years, was explained by Dai Qianhuan. Themechanism named di-region theory predicted that a carcinogen always metabolizes to form a specialbi-functional alky-lating agent. This agent induces cross-linkages between the complementary basepairs in DMA and switches on initial mutageneses in genomes including point and frameshiftmutations. This, in turn, induces further deep mutageneses including the production of variouschimeric chromosomes, deletions and other aberrations found in genomes. In the end this initiatescarcinogenesis of the whole cell through the reverse transcription mechanism after a lengthyincubation period. Recently, this laboratory has verified that physical carcinogenesis, includingthe oncogenesis induced by radiation and asbestos as well as the carcinogenesis induced byendogenous factors such as estrogen or diethyl-stilbestrol switch on carcinogenesis by inducing theformation of cross-linkages between the complementary base pairs in DNA. Di-region theory has nowbeen supported by many experimental observations such as mutational spectra of various carcinogens.The potential for carcinogenesis, teratogenesis, sterility and mutagenesis lumped together asgenetic toxicity appears to originate almost uniformly from the cross-linking between complementarybases, i.e. malignant cross-linking, which is in accordance with di-region theory. Other forms ofcross-linking between non-complementary bases, benign cross-linkings, show bi-functional alkylationanticancer activity but lack genetic toxicity. The predictable design and synthesis of a highselectivity anticancer agent with high efficacy and low genetic toxicity, a goal long pursued incancer chemotherapy, have been realized for the first time in this laboratory by inhibitingmalignant and heightening benign cross-linking using the principles of di-region theory. A series ofpatented new anticancer platinum complexes called di-regioplatins, based on the above predetermineddesign, have been reported. In these cancer cell kill rates, tumor-inhibition rates and theultimate life-span for two mouse carcinoma models using several compounds ofcis-di-substituted-benzylaminodihaloplatinum (II) are notably higher than those of cisplatin, buttheir toxicities all are much lower than cisplatin. Based on a predictive design using di-regiontheory and group theory, a new anticancer complex,cis-diammine-cyclopentane-1,1-dicarboxylato-platinum (II) called minoplatin, has been synthesized inthis laboratory by making the minimal structural revision of adding an CH_2 unit on the four-memberring of carboplatin.
